Disulfiram as a radiation modifier
The radiation modifying effect and toxicity of tetraethylthiuram disulfide (disulfiram) have been studied. Disulfiram (DSM) inhibits aldehyde dehydrogenase, dopamine-beta-oxygenase, microsomal mixed-function oxidases and cytochrome P-450 enzymes. It is widely used for aversion therapy in alcoholism. Disulfiram also inhibits tumor formation by several known carcinogens. A biphasic toxicity pattern of DSM is reported in the L-929 mouse fibroblast culture system. Disulfiram is 100 percent toxic at 2 X 10(-7) M (0.05 micrograms per ml), 23 percent toxic at 3 X 10(-7) M (0.1 microgram per ml), and 100 percent toxic again at 3.4 X 10(-6) M (1.0 microgram per ml). The pattern is similar to the biphasic toxicity pattern of DMS's major metabolite, sodium diethyldithiocarbamate (DTC). Reports of both radiation protection and radiation enhancement by DTC exist. Previously, a radioprotective effect by 2 X 10(-6) M DTC (dose modifying factor = 1.26) has been demonstrated in the L-929 cell system. To date, no radiation modifying properties of DSM have been reported. Our investigation of DSM as a radiation modifier at 3 X 10(-7) M (0.1 microgram per ml) did not show significant improvement in survival of irradiated cells treated with DSM relative to the irradiated control group, as determined by absence of a difference in the Do of the two groups. Considering DSM's close structural relationship to DTC, it is possible that DSM may exhibit a radioprotective effect when applied in a different concentration than what was used in our research.
- Research Organization:
- Univ. of Arkansas for Medical Sciences, Little Rock
- OSTI ID:
- 6776949
- Journal Information:
- Ann. Clin. Lab. Sci.; (United States), Vol. 6
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
DISULFIDES
RADIOSENSITIVITY EFFECTS
ENZYME INHIBITORS
L CELLS
METABOLITES
MICE
RADIATION PROTECTION
TOXICITY
ANIMALS
MAMMALS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
RODENTS
VERTEBRATES
560120* - Radiation Effects on Biochemicals
Cells
& Tissue Culture